Background: Onychomycosis is a fungal infection of the nail plate that is persistent in its nature and is known to have a poor response to drugs because of poor penetration of drugs through the bulky keratinized barrier. Ethosomal nanocarriers are phospholipid-based and have a high ethanol content to provide a superior membrane fluidization and deformability, thus becoming a potential solution to improving transungual drug delivery.

Aim: The purpose of this study was to design,urethrate and test an ethosomal-based Efinaconazole transungual delivery system to increase drug permeation, retention and antifungal activity as an effective means of onychomycosis treatment.

Methods: The ethosomes of efinaconazole were prepared by a thin-film hydration method and optimized with the help of a Box and Behnken Design taking into account the concentration of lecithin, ethanol, and cholesterol as independent variables. Dependent responses were a trapment efficiency, vesicle size and cumulative drug release. The optimized ethosomes were described by FTIR, DSC, XRD analysis, vesicle size and zeta potential, estimation of the drug content, viscosity and spreadability, in-vitro diffusion tests and antifungal activity against Candida albicans. The stability studies were performed in ICH accelerated conditions.

Results: Ethanol ethosolubility studies proved that Efinaconazole had maximum solubility in ethanol, and ethosolubility was appropriate. Optimization on BBD provided excellent fit of the model (R 2 > 0.97) with lecithin and ethanol having a significant effect on vesicle properties and drug release. Compared to the marketed formulations the optimized formulation had high entrapment efficiency, homogenous vesicle morphology, negative zeta potential, superior in-vitro permeation, and enhanced antifungal activity. The outcome of formulation was good.

Conclusion: Optimized ethosomal formulation demonstrated both high potential and high performance in terms of Efinaconazole permeation and antifungal effect, which indicates significant promise as a transungual delivery system to use as an agent that treats onychomycosis.

KEYWORDS: Efinaconazole, Ethosomes, Transungual Delivery, Onychomycosis, Antifungal Activity.